Tuesday , October 19 2021

The key to a long life has little to do with "good genes"



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In 2013, Google Co-founder and CEO Larry Page announced the formation of a new alphabetical entity dedicated to the resolution of the mortality enigma. Since then, the longevity laboratory of millions of dollars known as Calico-short for the California Life Company-has been trying to separate the fundamental biology of aging with the hope of one day of overcoming death. The hyper-secretive research company has published some details about what it really does within the Silicon Valley laboratory, but there have been indications. One of the company's first contracts was the renowned geneticist Cynthia Kenyon, a researcher at UC San Francisco who for 20 years doubled the life of a laboratory mange by launching a single letter in his DNA.

Shortly after joining Calico, Kenyon recruited a postgraduate UCSF bioinformatics called Graham Ruby. He did not want to dig into the genetics of the worm or study the company colony of naked wet naked rats. I wanted to ask a much wider question for the first time: how great a role of genes is, in any case, to determine how long someone lives? Other scientists have tried to ask that question before, with contradictory results. To erase things, you need to get a lot more information. Thus, Calico has been the largest family history database in the world: consumer genetics and genealogy of the company Ancestry.

In 2015, companies include a research association to investigate human life's inheritance, and Ruby leads the burden to leak the immense forest of family trees. What he found when analyzing the pedigrees of more than 400 million people who lived and died in Europe and America, dating back to 1800 was that although longevity usually runs in families, his DNA has less influence on how long he lives in what was thought The results, published on Tuesday in the magazine Genetics, is the first public research carried out by the collaboration, which ended silently in July and whose terms remain confidential.

"The true inheritance of human longevity for this cohort is probably no more than seven percent," says Ruby. The previous estimates on what the genes explain the variations in their useful life varied between 15 and 30 percent. So what left Ruby find that previous studies had lost? How many times human beings go against the old adage that "opponents attract".

It turns out that, through each generation, people are much more likely to select peers with similar lifetimes than random predictions. The phenomenon, called "assortive mating", could be based on genetics or sociocultural traits or both. For example, you can choose a partner who also has curly hair, and if the short hair stroke becomes associated to a long distance, this would inflate the estimates of the inheritance of life transmitted to your children. The same for non-genetic features such as wealth, education and access to good health care. People tend to choose partners in the same income range with the same degree of terminal, the two are associated with living longer and healthier lives.

The first indication that something other than genetics or a shared family environment could be at work when Ruby tried to get acquainted with the relatives of lawyers. His analysis began with a set of family trees consisting of 400 million individuals. The data were clean, unidentified and sewn by geneticists and computer scientists in Ancestry based on public information generated by a subscriber. Using the basic laws of inheritance, everyone inherits half their DNA from one parent and half the other, repeated in generations. Ruby's team analyzed the relationship between two people and how long they lived. They investigated parent-child pairs, couples, several cousins, and so on. There was nothing surprised there.

But when Ruby looked at his laws, things began to be weird. Logic suggests that you should not share significant DNA fragments with the spouse of your siblings, such as your brother's wife or her sister's husband. But in Ruby's analysis, people connected through a couple of close relatives were almost as likely to have similar lifetimes as people connected through the blood. "I get caught up in surprise by this," says Ruby. "Although no one has shown the impact of assortment mating to such an extent before, it aligns well with the way we know that human societies are structured."

Research can affect the whole field of longevity studies. Ruby says that it does not invalidate any prior work in the identification of individual genes involved in aging or in age-related diseases, but suggests that finding more of these genes will be much harder to follow. To find them, scientists will need huge cohorts to achieve sufficient statistical power. This should not be a problem for Calico, which in addition to family trees also had access to unidentified DNA information from millions of Genotics Ancestry clients as part of the research association.

Companies have at least one more document about the genetics of longevity currently under peer review. An Ancestry spokesman said that according to the original terms of the agreement, the association between him and Calico concluded with the presentation of the investigation that covers these findings. Calico is free to pursue the leads that arose from the analysis, but the company is not saying anything about what they can be at this time. (The spokesman for Calico declined to comment on the collaboration of Ancestry beyond the results of today's publication).

For now, the great place of conservation seems to be that humans have more control over how long they live than their genes. They are all the other things that families share houses and neighborhoods, culture and cuisine, access to education and health care, which make a much greater difference in the set of numbers that one day can grace their gravestone.

Maybe that's why ancestry scientist Catherine Ball claims that the company has no plans to offer a longevity score in any of its DNA test products at any time. "Right now, a healthy life seems to be more of a function of the options we make," she says. She points to places in the data where life times have had great successes – for males during the First World War – and then in two waves in the second half of the twentieth century as men and then women took a habit of cigarettes.

"Do not smoke, and do not go to war. These are my two tips," she says. And maybe it takes time to exercise. Ball already has a Tuesday morning training painted on his calendar. This time, she says, she will not cancel her at the last moment.


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